Exogenous Ketone Esters for Refractory Status Epileptics

NCT ID: NCT05674552

Last Updated: 2024-11-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-01-10

Study Completion Date

2025-07-01

Brief Summary

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This study aims to investigate the efficacy of add-on exogenous ketone esters for the treatment of children with refractory generalized convulsive status epilepticus

Detailed Description

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Generalized convulsive status epilepticus (GCSE) is a common neurological emergency in children with significant morbidity and mortality. Benzodiazepines (Bzs) are the initial anti-seizure medications (ASMs) for children with GCSE, but nearly a third of cases are not controlled by (Bzs). Moreover, about 40% of cases not responding to BZs are not controlled by second-line ASMs.

Ketogenic diet (KD) has been classically used for treating children with drug resistant epilepsy. Recently, KD has been used for refractory and super refractory status epilepticus. However, KD takes time to achieve ketosis and may be practically challenging in emergency situations and critically ill patients. Exogenous ketone esters (EKE) could be a more convenient and rapid way to achieve ketosis in acute settings.

Conditions

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Status Epilepticus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Eligible children will be randomized into two equal-sized groups. Study group: will receive exogenous ketone esters plus standard of care. Control group: will receive only standard of care.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Study group

Children receiving exogenous ketone esters + standard of care

Group Type EXPERIMENTAL

Exogenous ketone ester

Intervention Type DRUG

500 mg/kg over 5 min administered by nasogastric tube, followed after 1 hr by repeated hourly doses of 125 mg/kg for 8 hrs.

Control group

Children receiving only standard of care

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Exogenous ketone ester

500 mg/kg over 5 min administered by nasogastric tube, followed after 1 hr by repeated hourly doses of 125 mg/kg for 8 hrs.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Refractory Generalized convulsive status epilepticus.

Exclusion Criteria

* Failure to obtain informed consent.
* Recent intake of exogenous ketones, ketogenic diet, or any dietary restrictions/modifications.
* Hemodynamic or cardio-respiratory instability.
* Traumatic brain injury.
* Hypo-/hyperglycemia.
* Metabolic acidosis.
* Ketosis (βHB \> 2 mmol/L).
* Associated severe disease condition, including hepatic, renal, respiratory, cardiac, gastrointestinal, endocrinal, and immune systems.
* Malnutrition/obesity.
* Limitations to nasogastric tube feeding.
* Inborn errors of metabolism.
* Allergies or any other contraindication to exogenous ketone esters.
* Current or recent (within the last 24 hours) propofol therapy.
* Intake of carbonic-anhydrase inhibitors.
Minimum Eligible Age

1 Year

Maximum Eligible Age

10 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sohag University

OTHER

Sponsor Role lead

Responsible Party

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Elsayed Abdelkreem

Lecturer of Pediatrics

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Abdelrahim A Sadek, MD, PhD

Role: STUDY_CHAIR

Sohag University

Locations

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Department of Pediatrics at Sohag University Hospital

Sohag, , Egypt

Site Status RECRUITING

Countries

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Egypt

Central Contacts

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Elsayed M Abdelkreem, MD, PhD

Role: CONTACT

01114232126

Facility Contacts

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Abdelrahim A Sadek, MD, PhD

Role: primary

References

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Arya R, Peariso K, Gainza-Lein M, Harvey J, Bergin A, Brenton JN, Burrows BT, Glauser T, Goodkin HP, Lai YC, Mikati MA, Fernandez IS, Tchapyjnikov D, Wilfong AA, Williams K, Loddenkemper T; pediatric Status Epilepticus Research Group (pSERG). Efficacy and safety of ketogenic diet for treatment of pediatric convulsive refractory status epilepticus. Epilepsy Res. 2018 Aug;144:1-6. doi: 10.1016/j.eplepsyres.2018.04.012. Epub 2018 Apr 27.

Reference Type BACKGROUND
PMID: 29727818 (View on PubMed)

Chomtho S, Uaariyapanichkul J, Chomtho K. Outcomes of parenteral vs enteral ketogenic diet in pediatric super-refractory status epilepticus. Seizure. 2022 Mar;96:79-85. doi: 10.1016/j.seizure.2022.01.019. Epub 2022 Feb 5.

Reference Type BACKGROUND
PMID: 35158320 (View on PubMed)

Clarke K, Tchabanenko K, Pawlosky R, Carter E, Todd King M, Musa-Veloso K, Ho M, Roberts A, Robertson J, Vanitallie TB, Veech RL. Kinetics, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in healthy adult subjects. Regul Toxicol Pharmacol. 2012 Aug;63(3):401-8. doi: 10.1016/j.yrtph.2012.04.008. Epub 2012 May 3.

Reference Type BACKGROUND
PMID: 22561291 (View on PubMed)

Gilbert DL, Pyzik PL, Freeman JM. The ketogenic diet: seizure control correlates better with serum beta-hydroxybutyrate than with urine ketones. J Child Neurol. 2000 Dec;15(12):787-90. doi: 10.1177/088307380001501203.

Reference Type BACKGROUND
PMID: 11198492 (View on PubMed)

Schoeler NE, Simpson Z, Zhou R, Pujar S, Eltze C, Cross JH. Dietary Management of Children With Super-Refractory Status Epilepticus: A Systematic Review and Experience in a Single UK Tertiary Centre. Front Neurol. 2021 Mar 12;12:643105. doi: 10.3389/fneur.2021.643105. eCollection 2021.

Reference Type BACKGROUND
PMID: 33776895 (View on PubMed)

Si J, Wang Y, Xu J, Wang J. Antiepileptic effects of exogenous beta-hydroxybutyrate on kainic acid-induced epilepsy. Exp Ther Med. 2020 Dec;20(6):177. doi: 10.3892/etm.2020.9307. Epub 2020 Oct 9.

Reference Type BACKGROUND
PMID: 33101467 (View on PubMed)

Stubbs BJ, Cox PJ, Evans RD, Santer P, Miller JJ, Faull OK, Magor-Elliott S, Hiyama S, Stirling M, Clarke K. On the Metabolism of Exogenous Ketones in Humans. Front Physiol. 2017 Oct 30;8:848. doi: 10.3389/fphys.2017.00848. eCollection 2017.

Reference Type BACKGROUND
PMID: 29163194 (View on PubMed)

Carson RP, Herber DL, Pan Z, Phibbs F, Key AP, Gouelle A, Ergish P, Armour EA, Patel S, Duis J. Nutritional Formulation for Patients with Angelman Syndrome: A Randomized, Double-Blind, Placebo-Controlled Study of Exogenous Ketones. J Nutr. 2021 Dec 3;151(12):3628-3636. doi: 10.1093/jn/nxab284.

Reference Type BACKGROUND
PMID: 34510212 (View on PubMed)

Cox PJ, Kirk T, Ashmore T, Willerton K, Evans R, Smith A, Murray AJ, Stubbs B, West J, McLure SW, King MT, Dodd MS, Holloway C, Neubauer S, Drawer S, Veech RL, Griffin JL, Clarke K. Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes. Cell Metab. 2016 Aug 9;24(2):256-68. doi: 10.1016/j.cmet.2016.07.010. Epub 2016 Jul 27.

Reference Type BACKGROUND
PMID: 27475046 (View on PubMed)

Trinka E, Cock H, Hesdorffer D, Rossetti AO, Scheffer IE, Shinnar S, Shorvon S, Lowenstein DH. A definition and classification of status epilepticus--Report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia. 2015 Oct;56(10):1515-23. doi: 10.1111/epi.13121. Epub 2015 Sep 4.

Reference Type BACKGROUND
PMID: 26336950 (View on PubMed)

Other Identifiers

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Soh-Med-22-12-46

Identifier Type: -

Identifier Source: org_study_id